It is known that various protein kinases exist in vivo and are involved in the regulation of a variety of functions. Bruton's tyrosine kinase (BTK) is a protein kinase that belongs to Tec kinase family, which is expressed in myeloid cells such as B-cells, monocyte/macrophages, neutrophils, mast cells and osteoclasts, and is involved in regulating functions of these cells (Non-Patent Literatures 1 and 2). BTK is located in the downstream of the immunereceptor signals such as B-cell receptor (BCR) or Fc receptor (FcR) family, being involved in the proliferation, survival, differentiation and activation of B-cells, and involved in regulating expression of inflammatory cytokines (for example, tumor necrosis factor-α or interleukin-1β) or chemical mediators (for example, histamine or leukotriene) in monocyte/macrophage or in mast cells (Non-Patent Literature 3). An inhibitor capable of regulating BTK activity is considered to be useful as a therapeutic agent for diseases associated with abnormal hyperactivity of BTK signaling pathway (for example, cancer, allergic diseases, or autoimmune diseases).
In recent years, it has been considered that, in addition to B-cells which are involved in antibody production, various cells such as monocytes/macrophages, neutrophils, mast cells and osteoclasts, which express Fc receptor (FcR) family or its related molecules, are closely associated with incidence or progress of autoimmune diseases such as rheumatoid arthritis (Non-Patent Literature 4). Since BTK signals are associated with activation of these cells or abnormal activation of functions thereof (Non-Patent Literatures 2 and 3), it is expected that a compound with BTK inhibitory effect has a therapeutic efficacy against autoimmune diseases. In addition, since BTK is also involved in activation of mast cells, it is expected that a compound with BTK inhibitory effect has a therapeutic efficacy against allergic diseases with which B-cells or mast cells are associated.
Currently known BTK inhibitors include PCI-32765 (Non-Patent Literature 5) and the compounds described in Patent Literatures 1 and 2 (Patent Literatures 1 and 2). The PCI-32765 is known to inhibit EGFR as well as BTK, and to be a compound useful as a therapeutic agent for immune diseases (such as rheumatoid arthritis) (Non-Patent Literature 5).
Meanwhile, it is known that EGFR binds to, for example, epidermal growth factor (EGF) which is a ligand, and participates in the proliferation and survival (for example, inhibition of apoptosis) of various cells (Non-Patent Literature 6). It is known that inhibitors targeting EGFR cause adverse effects such as skin disorders and gastrointestinal dysfunction in common, and it is widely supposed that these adverse effects may be related to the inhibition of the wild type EGFR signaling pathway (Non-Patent Literature 7), and therefore, an inhibitor which has a high BTK selectivity and is highly useful has been desired as a preventive and/or therapeutic agent of immune diseases.